Epirubicin Regimen Cuts Risk of Death in Premenopausal Women With Early Breast Cancer

Premenopausal women with early breast cancer
have a significantly better chance of living longer when treated with
a chemotherapy regimen that includes epirubicin (Ellence), as opposed
to a current standard combination regimen, according to data
presented at the 35th meeting of the American Society of Clinical
Oncology (ASCO).

In a large phase III study involving more than 1,000 women,
researchers demonstrated that adjuvant treatment with the CEF regimen
(cyclophosphamide, epirubicin, and fluorouracil) improved 6-year
survival rates in premenopausal women with node-negative, grade 2-3
tumors. Patients treated with the epirubicin combination achieved a
survival rate that was 10% higher (93% vs 83%; P < .01) than the
rate achieved with the commonly used drug combination CMF
(cyclophosphamide, methotrexate, and fluorouracil).

This study shows that an epirubicin-based regimen offers highly
significant disease-free and overall survival advantages for
premenopausal breast cancer patients compared to a CMF regimen,
said Dr. Henning Mouridsen, principal trial investigator and general
secretary at the Danish Breast Cancer Cooperative Group, Copenhagen
University Hospital, Denmark. By using the epirubicin-based
regimen instead of CMF, we can decrease the risk of death from breast
cancer in premenopausal women by approximately 20% to 25%.

The epirubicin combination and CMF are standard treatments
around the world, so this study is of special importance, said
Dr. Mouridsen. Although 10-year data will offer a true test of
the treatments success, the 6-year survival data is very promising.

Clinical Trial Design

The trial followed 1,195 premenopausal and postmenopausal women with
early breast cancer for 6 years. Enrollees fell into one of three
subgroups: premenopausal women with node-negative, grade 2-3 tumors
(subgroup A); premenopausal women with node-positive,
receptor-negative or receptor-unknown tumors (subgroup B); and
postmenopausal women with node-positive, receptor-negative tumors
(subgroup C). Following surgery, patients were randomly assigned to
receive first-line chemotherapy with either CMF or CEF.

After 6 years, the combined overall survival rate in
epirubicin-treated women from subgroups A and B was 76%, compared to
69% (P < .01) for those given the CMF combination. (A 24% death
rate for the CEF arm compared to a 31% death rate for the CMF arm
results in an absolute mortality reduction of 7% and a relative
reduction of approximately 20% to 25%.) In subgroup A, women treated
with CEF had a survival rate of 93%, while those receiving CMF had a
survival rate of 83% (P < .01). Women in subgroup B who were
treated with CEF had a survival rate of 66% vs a 60% survival rate
for those given CMF. No statistically significant difference in
survival rates between treatments was observed in subgroup C (50% vs 48%).

Toxicities Evenly Distributed

Hematologic toxicities were evenly distributed in the two groups.
Side effects that occurred more frequently in the CEF group included
transient hair loss (87% vs 7%) and loss of menstrual function (80%
vs 60%).

The study results concerning epirubicin will have a major
impact on the management of breast cancer, said Dr. Mouridsen.
Except in the United States, where epirubicin has not yet been
approved,* women with early breast cancer are generally treated with
a regimen based on either epirubicin or methotrexate. This study
shows that epirubicin may be the better treatment option for
premenopausal women.

In the United States, two standard chemotherapy regimens, CMF and CAF
(cyclophosphomide, Adriamycin, and fluorouracil), have demonstrated
similar survival rates when used as adjuvant treatment.

*Editors Note: Since the ASCO meeting, epirubicin has
received approval in the United States for the treatment of breast cancer.